Isolated hepatocytes will be utilized as a research tool to investigate further the lipid peroxidation theory of aging. Both freshly isolated hepatocytes and hepatocytes maintained in culture obtained from young, adult and old rats will be evaluated for their functional and structural integrity. Subsequently these cells will be evaluated for rates of lipid peroxidation utilizing both the thiobarbituric acid assay and chemiluminescence. Isolated hepatocytes will also be evaluated in terms of their peroxidation defense systems. Specifically cells isolated from young, adult and old rats will be evaluated for levels of A) antioxidants such as vitamin E and gluthatione, B) glutathione peroxidase and C) superoxidase dismutase. As a further assessment of the cellular peroxidation defense system, isolated hepatocytes will be subjected to low levels of induced lipid peroxidation and subsequently evaluated for cell injury in terms of: A) leakage of lactic dehydrogenase, B) levels of glucose-6-phosphatase and C) capacity to respond to glucagon. Finally, isolated hepatocytes will be incubated for several days in the presence of substances postulated to alter the aging process (such as antioxidants, cortisone, and procaine-HCL). Hepatocytes will then be evaluated for: A) rates of lipid peroxidation, B) cellular injury, C) antioxidant levels and D) susceptibility to peroxidation-induced injury. This study will help to clarify whether rates of lipid peroxidation are significantly different in young and old animals and further whether a fundamental difference exists in the cellular peroxidation defense systems of young and old animals.